The murine and human cellular analogues of an avian retroviral transforming gene (c-myc) have been directly associated with chromosome translocations commonly observed in murine plasmacytomas (t(12;15)) and Burkitt lymphomas (t(8;14)). We propose to continue and extend our studies of the molecular basis and consequences of myc gene activation for B lymphoid cell transformation. Different molecular targets for myc rearrangements in murine plasmacytomas will be localized and their structures and significance for myc expression determined. Novel myc RNAs activated by translocation will be studied at the cytoplasmic and nuclear RNA levels. Transcription start sites will be mapped by primer extension synthesis strategies. The activities of promoter and potential enhancer elements will be assessed by their ability to drive the expression of a fused gene (i.e., chloramphenicol acetyl transferase or CAT) in fibroblasts and different lymphoid cell types. Modified myc genes will be stably integrated into lymphoid tumor cells which express either normal or truncated myc RNAs. The resultant effect(s) on normal and cryptic myc promoter activities will be determined. The activity of transfected and endogenous myc genes will also be compared in these transfected cells with myc exon and intron specific probes. These experiments will allow us to investigate potential cis or trans systems for regulating myc expression. The contributions of dual promoters for elevated c-myc expression in lymphosarcomas and plasmacytomas will be determined. Finally, murine retroviral vectors containing either activated myc or human ras oncogenes will be introduced into normal proliferating B cells and their effects on growth factor dependency analyzed. These experiments would allow us to develop a B-cell transformation system which is dependent on the presence of a translocation activated myc gene. (X)